Treatment of a disease or a condition with a biologic compound presents a number of challenges. One of them is to determine which patient population is eligible for a particular treatment, which subjects are going to respond to this treatment and which subjects will lose response after a certain amount of time. This information has significant impacts upon further patient's care and clinical study designs.
Biomarkers are usually helping for answering these questions.
A biomarker may be defined as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic intervention”.
In the art, a great number of studies describe the use of molecules such as cytokines or the use of gene expression profiles to determine whether or not the treated subject is going to be a responder to the treatment.
For example, molecules such as CRP and cytokines such as IL-1 beta, IL-2, IL-6, IL-8, IL-12 or interferon gamma have been described as biomarkers to define the response of subjects with Crohn's disease to infliximab and other biologic compounds. WO2008/147869 describes the determination of at least one gene expression among IP-10, MCP-1, MMP-9, TNF alpha, EGF, IL-6, ENA-78, MPO, MIP-1 beta and VEGF for evaluating the efficacy of a treatment for gastro-intestinal disorders. WO2008/048986 also relies on measuring expression of genes selected in a list for classifying individuals as responder or non-responder to a treatment for inflammatory bowel diseases. Another example is EP2056110 describing the detection of specific proteins to assess the responsiveness to an anti-TNF treatment.
The present invention relates to Tr1 cell therapy used for treating chronic inflammatory diseases, autoimmune diseases, allergic diseases, and organ transplantation conditions. As shown previously, Tr1 cells can be used for treating multiple sclerosis (WO2009052283), intestinal inflammatory conditions such as Crohn's disease (WO2009068575) or arthritic conditions such as rheumatoid arthritis (WO2009054242).
Although biomarkers have been described for evaluating the outcome of therapies against those conditions, there is a need for biomarkers that will specifically allow the prediction of the outcome of a Tr1 cell therapy. There is a need for stratification of patients who are being subjected to a Tr1 cell therapy and for distinguishing between Tr1 cell therapy responder and non responder patients.